Bimodal Dissolving Microneedles with Nanoparticle Coating and Encapsulation for Extended Dual-Drug Delivery

Effective co-delivery of multiple drugs via microneedle (MN) platforms is challenging due to limited loading capacity and the need for sustained release. This study presents a bimodal coated-dissolving microneedle (DMN) patch for extended delivery of diclofenac (DCF) and dexamethasone (DSP) nanoparticles to treat osteoarthritis. The DMN tips are loaded with DCF nanoparticles (3.84 mg/patch) and coated with DSP-PLGA nanosuspensions (0.44 mg/patch), achieving dual-drug release from a single patch. Ex vivo studies in neonatal porcine skin show > 90% penetration into the stratum corneum (≈276 µm depth), with transdermal delivery of 1.54 mg DCF and 118 µg DSP at 24 h. In vivo pharmacokinetic studies in rats demonstrate sustained DCF plasma levels for 72 h, with an extended half-life (13.0 h) and 80.3% relative bioavailability compared to oral dosing. DSP exhibits a biphasic release, peaking at 24-30 h (227.7 ng mL^-1, 63.9% bioavailability). High drug levels persist in skin and paw tissues for 72 h, suggesting prolonged local efficacy. These bimodal DMNs provide a high-loading, sustained-release platform for minimally invasive, patient-friendly dual-drug therapy, optimizing osteoarthritis treatment and improving compliance.